Immunoligical Tolerance

Question 1

Immunological Tolerance

Answer 1

Failure to respond to an Ag delivered via a protocol that would normally be expected to induce an immune response

Question 2

Newborn animals have long gestation period hence their acquired system is fully developed, _____________

Answer 2

But limited or not functional

Question 3

What are newborns dependent on ?

Answer 3

Immunity in the form of T cells and Abs from the mother during the first weeks
They suppress the newborn immune system

Question 4

What is arterial transfer of Abs dependent on?

Answer 4

Type of placenta
Pigs, horses, ruminants: no transfer
Dogs and cats: 5-10% IgG

Question 5

What does functionality of immune response depend on?

Answer 5

Antigenic stimulation (limited in fetus)

Question 6

Neonatal tolerance

Answer 6

Exposure to an antigen in utero or during early neonatal life –> challenge with that antigen later in life fails to trigger an immune response

Question 7

Neonatal tolerance example

Answer 7

Bovine viral diarrhea virus (BVDV)
An infection during fetal development results in PI infected calves
Cytopathic and non cytopathic

Question 8

Tolerance in fetus and newborn infected with BVD

Answer 8

Fetal calf develops immune tolerance to the non-cytopathic strain
Continually viremic and shed virus (infect other animals)
Calf seronegative due to tolerance state
Other infected calves develop immune response

Question 9

What happens to a tolerant calf if infected by cytopathic strain?

Answer 9

It develops mucosal disease (no tolerant)
2-4 weeks-fatal

Question 10

Pre-vax induced tolerance in newborn

Answer 10

Inhibits the response of the puppies to the vaccine
B cell specific, T cells unaffected

Question 11

Adult tolerance

Answer 11

Induction of tolerance to a foreign antigen during adulthood by giving a single high dose or multiple lower doses of that antigen

Question 12

Adult-induced immune tolerance

Answer 12

Experimentally induced in lab animals against foreign Ags
Dependent on the dose of Ag given
High and low zone tolerance: act via the activation of Treg cells

Question 13

High Zone tolerance

Answer 13

T and B cell paralysis

Question 14

Low zone tolerance

Answer 14

T cell tolerance-leads to B cell tolerance

Question 15

Oral tolerance

Answer 15

Failure to respond to systemic immunization with an Ag following oral delivery of the same Ag
Not absolute

Question 16

Breakdown of oral tolerance

Answer 16

May lead to the development of food allergy or IBD

Question 17

What the is biological significance of oral tolerance?

Answer 17

Tolerance to food Ags, while the immune response fights against pathogens

Question 18

T regulatory cells (Treg)

Answer 18

Abundant in mucosae including the intestine (vital organ)
Large amount of soluble food proteins leads anergy by activation of Treg

Question 19

Treg in oral tolerance

Answer 19

Presents a challenge to vaccination by the oral route because vax have adjuvant which breaks OT
Exploited to express immune responses to autoimmune diseases

Question 20

What regulates Treg activity?

Answer 20

Gut flora

Question 21

What does reduced microbial exposure cause?

Answer 21

In gut it depressed Treg production leading to increased allergies and autoimmunity

Question 22

Tolerizing Ag is presented by ______________

Answer 22

Dendritic cells

Question 23

Variable outcome of oral tolerance

Answer 23

T cell apoptosis
Not fully activated (T cell anergy)
Induction of specific regulatory T cells
Trl and Th3 produce IL-2 and TGF-b

Question 24

Fetomaternal Tolerance

Answer 24

Maternal immune system tolerated against fetus’s paternal Ags

Question 25

What does the decidua of the placenta contain?

Answer 25

NK and CD8+ cytotoxic T cells that are expected to destroy the fetus

Question 26

What is he maternal and fetal immune system active in?

Answer 26

Abortions induced by pathogens (toxoplasma, chlamedia, listeria)
Causes disruption of the placental interface and fetal loss

Question 27

Active Immune regulation

Answer 27

Key event in survival of the fetus:
Activation IL-10 and TGF-b and inhibtion of TNF-a and IFN-y
Reduced MHC expression
Expression of Fas ligand (apoptotic death)
Significant Treg cells within the placenta

Question 28

Neonatal